Munc18-1 in secretion: lonely Munc joins SNARE team and takes control

SNARE proteins and the Sec1/Munc18 (SM) protein, Munc18-1, are essential components of the mammalian secretion machinery. Until recently, quite divergent working models existed for the central but rather isolated role of Munc18-1 in secretion and its relation to the SNAREs. New studies now solve old discrepancies, bring consensus among SM–SNARE interactions and emphasize how closely these proteins work together. Together, SM and SNARE proteins control each step in the exocytotic pathway as a team. Munc18-1 operates as the chief commander of the exocytotic SNARE team, making teamwork more efficient, working with specific team members on specific jobs, reducing promiscuity with members of noncognate teams, and adjusting team efforts as a function of recent history and environmental cues (presynaptic receptor activation). SNARE proteins and the Sec1/Munc18 (SM) protein, Munc18-1, are essential components of the mammalian secretion machinery. Until recently, quite divergent working models existed for the central but rather isolated role of Munc18-1 in secretion and its relation to the SNAREs. New studies now solve old discrepancies, bring consensus among SM–SNARE interactions and emphasize how closely these proteins work together. Together, SM and SNARE proteins control each step in the exocytotic pathway as a team. Munc18-1 operates as the chief commander of the exocytotic SNARE team, making teamwork more efficient, working with specific team members on specific jobs, reducing promiscuity with members of noncognate teams, and adjusting team efforts as a function of recent history and environmental cues (presynaptic receptor activation).